Angiogenesis plays a critical role in physiological conditions such as embryonic development, reproduction, tissue repair and bone remodeling. In contrast, angiogenesis is recognized as a common denominator underlying a variety of deadly and debilitating human diseases, including cancer, age-related macular degeneration (AMD) and various inflammatory diseases. Tumor angiogenesis has been demonstrated to facilitate cancer progression and metastasis in the microenvironment. Pathological angiogenesis is also the major cause of AMD, which is one of the most common irreversible causes of severe loss of vision in the elderly population. Neovascular-AMD is characterized by choroidal neovascularization (CNV) that invades the subretinal space, often leading to exudation and hemorrhage.
Neovascularization involves recruitment of circulating endothelial progenitor cells (EPCs) from bone marrow to hypoxia sites as well as sprouting of preexisting endothelial cells. EPCs are a population of cells in the circulation and carry out angiogenesis and vascular remodeling for their ability to differentiate into endothelia cells and form blood vessels. Late EPCs have merits of being more committed to endothelial lineage differentiation and contribute to angiogenesis. Moreover, early EPCs have been proposed to improve angiogenesis/vasculogenesis through the production of angiogenic cytokines (e.g. VEGF and IL-8), which might activate adjacent endothelial cells. Recently, EPCs reportedly mediate early tumor growth and late metastatic progression by intervening with the angiogenic switch. Accumulated evidences indicate that EPCs promote the neovascularization in ischemic hypoxia tissue during AMD. These findings establish the role of EPCs in pathological angiogenesis and support that EPC targeting therapies may be the promising strategy to block angiogenesis-related diseases.
Dipeptide dertivative Fmoc-10a (9H-fluoren-9-yl)methyl (S)-1-((R)-1-hydroxy-3-phenylpropan-2-ylamino)-3-methyl-1-oxobutan-2-ylcarbamate) is an aurantiamide derivative, which composed of phenylalaninol and phenylalanine, and were a major component of Zanthoxylum dissitum, Semiaquilegia adoxoides and Polygonum chinensis. Aurantiamides exhibited anti-bacterial, anti-inflammatory (Chiao-Ting Yen et al., European Journal of Medicinal Chemistry 44 (2009) 1933-1940), antioxidant, and anti-HIV effects. Recently, many dipeptides showed cytotoxic effects against cancer cells (Chiao-Ting Yen et al., European Journal of Medicinal Chemistry 45 (2010) 2494-2502). For example, Peptichemio (PTC) and Bortezomib (VELCADE®) were developed and marketed for treating cancer.